Semiconductor-based sensors have been used in many applications involving the detection of a wide variety of characteristics in a multitude of disciplines. For example, image sensor arrays are finding widespread use in biological assay applications such as gene expression analysis and DNA sequencing. In related applications, both CCD and CMOS mega-pixel array platforms have been used to simultaneously capture bioluminescence or fluorescence signals from millions of miniaturized reaction chambers.
Bioluminescence signals generally have very low bandwidths, and can be extremely small compared to background noise due to the miniaturization of reaction volumes. To achieve sufficiently high sensitivity in a bio-sensor array, sensor signals are digitized with a high absolute accuracy (low noise and high linearity). The conversion rate required is governed by the number of sensor elements.
One particular sensing application involves Pyrosequencing, which takes advantage of bioluminescence detection for determining the nucleotide incorporation into the DNA molecule. There are various devices suitable for bioluminescence detection. A sensitive detection device is the photomultiplier tube (PMT); however, the overall photon detection efficiency of PMT-based systems is limited to 1-4% by the optics and low quantum efficiency (10%) of PMTs. Also, PMTs are bulky, costly, and require high operating voltages (1000 VDC), which has presented challenges to their use in a low-power, massively parallel system.
Another type of photosensor is the CCD (charge-coupled device). CCDs employ a “bucket brigade” to serially shift out the photogenerated electrons accumulated at each photosite. This charge transfer mechanism is noise-less, which leads to very good signal-to-noise ratio (SNR). However, CCD devices are fabricated in a nonstandard semiconductor process and are not readily integrated with other analog or digital circuits. As a result, its image sensors achieve very high sensitivity, low noise, and high uniformity at the price of inflexibility, added complexity, and higher cost.
These and other issues have been challenging to sensor applications, and particularly challenging to the sensing of bioluminescence in DNA sequencing applications.